Coaxing stem cells to become bone tissue is one
of many potential applications of stem cell research that is being explored
around the world. At North Carolina State University, Dr. Elizabeth Loboa’s
research uses a unique approach to create bone tissue from adult stem cells.

Post-doctoral fellow Michelle Wall (right) and Dr. Elizabeth Loboa observe
images that indicate palladin is located in human mesenchymal stem cells. Loboa's
team was the first to prove that palladin is present in these cells. (Photo:
Roger Winstead)

In the Cell Mechanics Laboratory at NC State, Loboa,
assistant professor of biomedical engineering, and her research assistants use
fluid shear stress applied to human mesenchymal stem cells (hMSCs) that have
been seeded into a polymeric scaffold to grow bone tissue. Mechanical
loading, such as applying fluid shear stress, is a key factor in functional
tissue engineering of bone. However, research on mechanical loading using
this method has typically focused on macrofluidic devices. Loboa and her
team in a collaboration with Dr. Glenn Walker, an expert in microfluidics, are
testing the use of microfluidic devices as a means to apply fluid shear stress
to mesenchymal stem cells seeded in three-dimensional (3D) scaffolds. Microfluidics
could more easily enable researchers to analyze multiple shear stresses simultaneously
by allowing them to compare data from parallel tests concurrently while lowering
costs through reducing the amount of media, scaffold material, and the number
of cells needed for each shear stress experiment.

Dr. Elizabeth Loboa (left), graduate student Wayne Pfeiler and post-doctoral fellow Michelle Wall study images that indicate palladin is located in human mesenchymal stem cells. Loboa's team was the first to prove that palladin is present in these cells. (Photo: Roger Winstead)

Their most recent research studied the effects of
fluid shear stresses on hMSCs seeded in three-dimensional (3D) poly-l-lactic
acid (PLLA) scaffolds in a flow perfusion microfluidic chamber. They found
that the cells were able to survive and grow on the PLLA scaffold in the microfluidic
device while exposed to fluid shear stress. Results were presented at
the 2005 Summer Bioengineering Conference held June 22-26 in Vail, Colo.

The PLLA scaffolds were designed by Dr. Behnam Pourdeyhimi,
the William A. Klopman Distinguished Endowed Chaired Professor and associate
dean for industry research and extension for the College of Textiles at NC State. The
scaffolds provide a biocompatible form for the cells to adhere to during growth
and provide mechanical stability during the formation of new bone tissue.

“If mesenchymal stem cells can be harvested from
the patient and used to create replacement bone tissue, the resulting replacement
bone would be completely compatible with the native bone, avoiding rejection
and other issues such as lack of autologous bone tissue for harvesting associated
with present-day bone tissue replacements,” said Loboa.

Loboa’s team also announced a breakthrough in hMSC
research at the conference. Her team is the first in the world to prove
that palladin, a protein associated with the actin cytoskeleton, is present
in mesenchymal stem cells. Since palladin is important in cytoskeletal
organization, the team believes that this discovery could lead to clues about
how mechanical stimuli modulate hMSC differentiation into bone.

“Eventually this research could lead to the development
of a process to grow bone to replace damaged or lost bone in patients with osteoporosis
or other skeletal defects,” said Loboa. “One of the problems with these
degenerative bone diseases is the loss of mobility. We hope that by giving
patients new bone that matches their native bone, we can restore some of their
mobility.”

The hMSCs used in Loboa’s lab are harvested from
bone and bone marrow from patients at UNC hospitals and from fat tissue
harvested during surgeries also performed by UNC surgeons.